R. T. Brittain et al., in Brit. J. Pharm., 49, 158(1973) and N. J. Harper et al., in J. Med. Chem., 17, 1188 (1974), disclose some 1-amino-1-benzamidomethylcyclohexane analgesic compounds of the formulae ##STR2## wherein X is hydrogen, 4-F, 3,4-di-Cl,2-Cl, 3-Cl or 4-Cl and Me denotes methyl; ##STR3## where X is 4-fluoro, 3,4-dichloro or 2-Chloro or 4-Chloro; and ##STR4## where X is hydrogen or 3,4-dichloro.
Also, Harper et al., in U.S. Pat. No. 3,975,443, in which numerous patent and other publication references are cited, discloses a class of compounds of the formula ##STR5## but claims only 1-(3,4-dichlorobenzamidomethyl)-cyclohexyldimethylamine. These compounds are stated to have utility as oral analgesics.
In addition, Lednicer U.S. Pat. No. 4,065,573, issued Dec. 26, 1978, discloses analgesic compounds of the formula ##STR6## wherein X is oxo or ##STR7## wherein n is zero or 1, R.sub.1 is hydrogen or C.sub.1 to C.sub.8 -alkyl, R.sub.2 is inter alia hydrogen or C.sub.1 to C.sub.8 -alkyl, R.sub.4 is hydrogen or methyl, R.sub.5 is hydrogen, phenyl, --CH.sub.2 -alkenyl wherein alkenyl is of 2 to 4 carbon atoms, inclusive, or methyl; aryl (Ar-) is thiophene or ##STR8## wherein m is zero, one or two, and Y is halogen, CF.sub.3, C.sub.1 to C.sub.4 -alkyl, C.sub.1 to C.sub.4 -alkoxy, hydroxy, C.sub.3 to C.sub.6 -cycloalkyloxy, C.sub.2 to C.sub.4 -alkanoyloxy, C.sub.1 to C.sub.4 -alkylthio, or ##STR9## wherein Y' is halogen, --CF.sub.3, C.sub.1 to C.sub.4 -alkyl, C.sub.1 to C.sub.4 -alkyloxy, R.sub.1 is hydrogen, C.sub.1 to C.sub.8 -alkyl, R.sub.2 is hydrogen, C.sub.1 to C.sub.8 -alkyl, --CH.sub.2 -alkenyl wherein alkenyl is 2 to 8 carbon atoms, acetyl, cycloalkylalkyl having 3 to 6 carbons in the cycloalkyl and 1 to 3 carbons in the alkyl, .beta.-hydroxyethyl, carbethoxymethyl, C.sub.3 to C.sub.6 -cycloalkyl, ##STR10## and R.sub.3 is hydrogen, C.sub.1 to C.sub.5 -alkyl, and the acid addition salts thereof, among others. However, such compounds do not have geminal 1-amino-1-amidomethyl substituents similar to those described and claimed herein.
Lednicer/Szmuszkovicz U.S. Pat. No. 4,212,878 discloses some N-[1-Amino-4-(mono- or di-oxygen-group-substituted)cyclohex-1-yl)methyl]-phenylacetamide derivatives, e.g., 2-(3,4-dichlorophenyl)-N-[[8-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]dec-8-yl] methyl]acetamide, and their pharmacologically acceptable salts, which have analgesic properties with lower physical dependence liability than morphine or methadone, for use as analgesic drugs in mammalian animals including humans.
In addition, Szmuszkovicz U.S. Pat. No. 4,098,904 discloses some N-(2-aminocycloaliphatic)benzamides, e.g., N-methyl-N-[2-(N-pyrrolidinyl)cyclohexyl]-3,4-dichlorobenzamide, and their pharmacologically acceptable salts, but such compounds do not have the amino group and the amido group bonded through the same cycloaliphatic ring carbon atom.
Those skilled in the analgesic chemical and pharmacology arts continue to search for new and useful compounds which have good analgesic activity with minimum amounts of sedation side effects.